Angiogram-Derived Functional Tests Pre-TAVI: Simpler, Yes, but Warranted?

An angiography-derived assessment of the functional significance of coronary lesions appears to offer advantages over pressure wire-based physiologic testing in patients with severe aortic stenosis, a new study shows.

Overall, there was no significant difference in the number of ischemic lesions detected using Murray’s law-based quantitative flow ratio (μQFR), which estimates functional significance of coronary lesions from a single angiographic view, and pressure wire-based fractional flow reserve (FFR).

Additionally, μQFR was more accurate than the instantaneous wave-free ratio (iFR) in identifying ischemic lesions, report investigators.

“μQFR could provide a reliable alternative to pressure wire-based assessment, with the advantage of being derived from a single and costless angiographic projection, with no need for invasive coronary instrumentation nor for adenosine infusion,” write Simone Fezzi, MD MSc (University of Verona, Italy), and colleagues online September 15, 2023, in Circulation: Cardiovascular Interventions.

Interventional cardiologist Amer Ardati, MD, MSc (University of Illinois at Chicago), who wasn’t involved in the study, said that while there have been multiple prospective studies showing FFR can accurately determine CAD significance, the pressure wire-based technology requires maximal vasodilation and hyperemia, which are problematic in the context of severe aortic valve stenosis.  

“What’s been found that’s really interesting is that FFR underestimates lesion significance in patients with severe aortic stenosis,” Ardati told TCTMD. “That’s because of the . . . aortic valve stenosis causing elevations in left ventricular and diastolic pressure, which means that the microcirculation is under higher pressure than it would be had there been no aortic stenosis involved.”

Ardati noted that prior studies in TAVI-treated patients have demonstrated that FFR values are substantially lower after the aortic stenosis is relieved, which “tells us that the FFR value in severe aortic stenosis may not be as effective in determining whether a lesion is ischemic or not.”  

Rodrigo Bagur, MD, PhD (London Health Sciences Center/Western University, Canada), who also commented on the study for TCTMD, pointed to another challenge of FFR in this setting. “For a patient with severe aortic stenosis, there is always a concern when you inject adenosine—even more so when you have a right coronary artery [lesion]—that you can get a transient [atrioventricular] block. The patient can end up with low [cardiac] output or even have a bad complication like shock,” he added.

Like Ardati, Bagur said the results with μQFR looked promising, but pointed out that QFR is not widely available in all labs, nor have data supporting the technology been widely validated.   

Identifying Ischemic Lesions

Researchers used computational μQFR (AngioPlus Core, Pulse Medical), to estimate the physiologic significance of 198 coronary stenoses in 128 patients scheduled for TAVI. Wire-based reference measurements with FFR were available for comparison in all patients and iFR data was available for 148 patients. 

The number of ischemic lesions—defined as FFR ≤ 0.80 and μQFR ≤ 0.80—did not significantly differ with both testing methods (19.7% versus 19.2%, respectively), whereas iFR identified 44.6% of lesions as physiologically significant, based on an iFR ≤ 0.89. (P < 0.001 compared with FFR and μQFR).

Using an FFR ≤ 0.80 as the reference for identifying ischemia—iFR identified 77.0% of ischemic lesions pre-TAVI, significantly fewer than the 93.4% identified by μQFR (P = 0.001). Both iFR and μQFR did well at identifying lesions that wouldn’t pose problems, but μQFR was better than iFR for identifying significant stenoses prior to TAVI. Using the same tests following TAVI, μQFR again outperformed iFR for identifying functionally significant disease.

Researchers also assessed the diagnostic performance of angiography-derived microvascular resistance (AMR) with the conventional wire-based method in 42 arteries, concluding that AMR had good accuracy (90.5%) and moderate correlation with the index of microvascular resistance, with an area-under-the-curve (AUC) of 0.887.

Worth noting, said Bagur, is that the reference diameter of the vessels measured using μQFR was 2.80 mm and the minimum lumen diameter was 1.69 mm. These small vessels are likely not jeopardizing a large amount of myocardium, he pointed out, adding they would most likely be too small for stenting.

Clinical Context is Critical

As TAVI moves into younger patients, the question of what to do with stable CAD in patients being worked up for TAVI is increasingly on the minds of physicians. While TAVI has important benefits for patients with symptomatic severe aortic stenosis, PCI has not been shown to reduce the risk of hard clinical events in stable CAD, compared with medical therapy—a point hammered home by the ISCHEMIA trial.

Moreover, trials testing the treatment of stable CAD prior to TAVI have yielded results “very similar to the general stable ischemic heart disease population,” Ardati noted.

In the ACTIVATION trial, PCI prior to TAVI in patients with at least one significant coronary stenosis did not reduce the primary endpoint of all-cause mortality or hospitalizations at 12 months. Just last week, a new study showed that patients who undergo PCI as part of their pre-TAVI workup had a higher risk of late major bleeding and these bleeding events were an independent predictor of all-cause mortality.

In 2017, Bagur, along with lead author Rafail Kotronios, MD (University of Oxford, England), published a meta-analysis that showed coronary revascularization before TAVI offered no clinical advantage with respect to several patient‐specific clinical outcomes. In fact, PCI was associated with an increased risk of major vascular complications and 30‐day mortality.

“All the data regarding stable coronary artery disease, regardless of the presence of severe aortic stenosis, [shows] PCI doesn't improve outcomes.” Bagur said.

‘Picking at the Margins’

For Ardati, if a patient undergoes coronary angiography as part of the pre-TAVI workup, a novel computational technology derived from the angiogram, one that doesn’t require vasodilation and hyperemia to provide functional information on lesion significance, would be beneficial for operators. Getting that same information from a CT scan would be even better, he added.

In clinical practice, a younger patient with diabetes and multivessel CAD found to be functionally worrisome in a pre-TAVI work up should probably head to surgery for revascularization and aortic valve repair, he said. “On the other hand, if you have an older patient who has limited coronary disease but clearly has severe aortic stenosis, it may make sense to just treat the valve, leave the coronary disease, and then see how the patient does clinically,” said Ardati. “If the patient is fine, then you really don't have a reason to intervene on those lesions.”

Using advanced imaging and algorithms amounts to “picking at the margins” of lesions of intermediate or unclear significance and is not ideal, Ardati added. “We really need to be more thoughtful about not just the ischemic burden of individual lesions, but also the clinical context,” he said. “What is the total burden of ischemia? What are the symptoms? Where is the lesion we’re talking about? Those kind of considerations can get lost in the shuffle when we’re broadly speaking about revascularization of lesions in TAVR patients.”

Bagur said that their center, which performs roughly 300 TAVIs per year, has stopped requiring routine angiography prior to the procedure unless the patient has clinical features that warrant it. For those who do undergo angiography, PCI would be performed in proximal significant vessels, such as the LAD or right coronary artery, with significant stenosis.